A major area of interest of this program is to investigate the possible interaction of behavioral factors in the etiology and progression of cancer in man. Investigation of such interaction will be facilitated by the development and use of animal models. Utilizing an animal model relevant to such interactions, the role of glutathione (an endogenous compound which deactivates metabolites of some carcinogens and promotes the formation of toxic metabolites of other carcinogens and promotes the formation of toxic metabolites of other carcinogens) as a possible modulating factor in gastric carcinogenesis is examined. Gastric carcinogenesis may be subject to behaviorally related alterations. These studies led to the discovery that rat glandular stomach contains exceedingly high concentrations of reduced glutathione (GSH), a finding which has important implications for gastric carcinogenesis. Moreover, the additional finding of stress-induced decreases in GSH suggests a testable mechanism whereby stressors could modulate susceptibility to certain chemical carcinogens. We are exploring the possible utility of a restraint-stress model in rats as a method for the study of effects of stressor exposure on metabolic pathways relevant to the expression of the effects of chemical carcinogens.